title: Protective effect of photodegradation product of nifedipine against tumor necrosis factor alpha-induced oxidative stress in human glomerular endothelial cells.
abstract: Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nitrosonifedipine (NO-NIF) is metabolically and photochemically produced from nifedipine, and NO-NIF has been recognized as a contaminant of nifedipine because it has no antihypertensive effect. Treatment of tumor necrosis factor-α (TNF-α) suppressed the cell viability and facilitated the expression of Inter-Cellular Adhesion Molecule 1(ICAM-1) in human glomerular endothelial cells (HGECs) though, pretreatment of NO-NIF significantly recovered the TNF-α-induced cell damage to the same extent as Trolox-C did, and suppressed the ICAM-1 expression in a concentration dependent manner. In addition, NO-NIF inhibited the cell toxicity induced by cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, as effective as Trolox-c. These data suggest that NO-NIF is a candidate for a new class of antioxidative drug that protect cells against oxidative stress in glomerular endothelial cells.
authors.affiliation: Department of Pharmacology, Institute of Health Bioscience, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Fukuhara
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Yuya
authors.initials: Y
authors.lastname: Horinouchi
authors.forename: Soichiro
authors.initials: S
authors.lastname: Tajima
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kihira
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hamano
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001555:Benzene Derivatives / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D001555:Benzene Derivatives; D009603:Nitroso Compounds; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C539379:nitrosonifedipine; D009543:Nifedipine; C007164:cumene hydroperoxide